Microfluidic synthesis of ultra-small magnetic nanohybrids for enhanced magnetic resonance imaging

We have developed a core alloying and shell gradient doping strategy for the controlled surface modification of nanoparticles, realized by a coupled competitive reducing-nucleation and precipitation reaction controlled in microfluidic channels. Here it is extended in surface modification of Fe and CoFe nanoparticles by doping zinc oxide and aluminum oxide to form well-dispersed stable ultra-small Fe(1-x)Znx@Zn(1-y)FeyO-(OH)(z) and (CoFe)((1-x))Al-x@Al(1-y)(CoFe)(y)O-(OH)(z) nanohybrids as contrast agents for magnetic resonance imaging (MRI). They exhibit greatly enhanced T-1 weighted spin echo imaging and T-2 weighted spin echo imaging effects. Particularly, (CoFe)((1-x))Al-x@Al(1-y)(CoFe)(y)O-(OH)(z) nanohybrids give a T-1 relaxation rate (R-1) of 0.156 (mu g-CoFe mL(-1))(-1) s(-1) and a T-2 relaxation rate (R-2) of 0.486 (mu g-CoFe mL(-1))(-1) s(-1), much higher than the commercial gadopentetate dimeglumine (R-1 = 0.022 (mu g-Gd mL(-1))(-1) s(-1); R-2 = 0.025 (mu g-Gd mL(-1))(-1) s(-1)). The R-1 of (CoFe)((1-x))Al-x@Al(1-y)(CoFe)(y)O-(OH)(z) nanohybrids is also higher than superparamagnetic iron oxide (SPIO) nanoparticles (R-1 = 0.121 (mu g-Fe mL(-1))(-1) s(-1)). SPIO nanoparticles of 7.1 +/- 1.2 nm still show an excellent negative MRI contrast agent by the highest R-2 (5.07 (mu g-Fe mL(-1))(-1) s(-1)) and R-2/R-1 ratio (42) among these reagents.